Do Depakote (valproate), Thorazine (chlorpromazine), and Clozaril (clozapine) cause urinary incontinence?

Urinary Incontinence Associated with Depakote, Thorazine, and Clozaril

Yes, all three medications—Depakote (valproate), Thorazine (chlorpromazine), and Clozaril (clozapine)—can cause urinary incontinence, with clozapine having the strongest association with this side effect.

Medication-Specific Incontinence Risk

Clozaril (Clozapine)

• Clozapine has the strongest and most well-documented association with urinary incontinence among these medications
• Incidence rates show that approximately 30% of patients on clozapine experience urinary incontinence 1
• Typically occurs as nocturnal enuresis within the first 3 months of treatment 1
• Often resolves spontaneously but may require intervention 1
• The mechanism is likely related to clozapine's potent anti-alpha-adrenergic effects, which reduce urethral sphincter tone 2

Thorazine (Chlorpromazine)

• As an antipsychotic medication, chlorpromazine can cause stress incontinence due to sphincter weakness 3
• The alpha-blocking properties of antipsychotics contribute to reduced urethral resistance 4
• Women are particularly susceptible to this effect 3

Depakote (Valproate)

• The FDA label for valproate specifically lists urinary incontinence as a reported adverse effect in epilepsy trials 5
• Occurs in less than 5% of patients taking valproate 5
• May be part of the CNS effects profile of the medication 5

Mechanisms of Drug-Induced Incontinence

1. Reduced sphincter resistance:

   • Alpha-adrenergic antagonism (particularly with clozapine and chlorpromazine) 2
   • Leads to stress incontinence when bladder pressure exceeds sphincter resistance 3

2. CNS effects:

   • Sedation and altered central nervous control of voiding 5, 4
   • Confusion or altered mental status affecting normal toileting behavior

3. Bladder overactivity:

   • Some medications may increase detrusor muscle activity 4
   • Results in urgency incontinence

Risk Factors for Medication-Induced Incontinence

• Female gender: Women are more susceptible to drug-induced stress incontinence 2
• Concomitant medications: Patients taking multiple medications that affect urinary function are at higher risk 2
• Polypharmacy: Taking multiple medications significantly increases the risk (OR = 4.9) 6
• Pre-existing urinary symptoms: Patients with baseline urinary issues may experience worsening with these medications 6

Management Strategies

1. For clozapine-induced incontinence:

   • Ephedrine (alpha-adrenergic agonist) is highly effective, with 15/16 patients showing improvement within 24 hours in one study 2
   • Complete remission occurs in approximately 75% of cases 2

2. General approaches:

   • Consider medication alternatives when possible
   • Implement behavioral strategies (scheduled voiding, pelvic floor exercises) 7
   • Avoid concomitant medications that may worsen incontinence 6
   • Manage timing of medication administration (e.g., avoiding evening doses for medications causing nocturnal incontinence) 1

3. If medication cannot be discontinued:

   • Consider adding antimuscarinic agents for urgency incontinence, with solifenacin having the lowest risk for discontinuation due to adverse effects 8, 7
   • For stress incontinence components, pelvic floor muscle training may help 7

Important Clinical Considerations

• Patients may be embarrassed and reluctant to report incontinence; specific inquiry may be necessary 1
• Incontinence is documented in medical records less frequently than it occurs 1
• Incontinence can significantly impact medication adherence and quality of life 1
• The risk-benefit ratio should be carefully considered, especially with clozapine, which may be essential for treatment-resistant schizophrenia despite side effects 2

Monitoring and Follow-up

• Actively inquire about urinary symptoms when prescribing these medications
• Monitor closely after initiation or dose changes of these medications 4
• Consider urological evaluation if symptoms persist despite management attempts

Understanding these medication effects on urinary function is essential for appropriate patient counseling and management of this potentially distressing side effect.